BackgroundHigh-altitude hypoxia disrupts intestinal homeostasis by impairing the epithelial barrier, triggering inflammation, and promoting microbial translocation. Berberine (BER), a natural isoquinoline alkaloid with antimicrobial and anti-inflammatory properties, has shown potential in protecting intestinal integrity; however, its efficacy under hypoxic conditions and its interaction with the gut microbiota remain unclear.MethodsA chronic hypoxia mouse model was used to investigate the protective effects of BER against intestinal injury.
Microbiota dependency was assessed through antibiotic-mediated depletion and fecal microbiota transplantation (FMT), combined with 16S rRNA gene sequencing, metabolomics, and immune profiling. The functional role of a BER-responsive bacterium was validated by oral administration in antibiotic-treated mice.ResultsBER supplementation restored epithelial barrier integrity, including tight junctions, antimicrobial peptide expression, and goblet cell function, while reducing inflammation and epithelial apoptosis under hypoxic conditions.
BER also reshaped gut microbial composition and network structure, accompanied by coordinated alterations in cecal metabolites, particularly purine metabolites and bile acids. Microbiota depletion abolished the protective effects of BER, whereas FMT from BER-treated donors recapitulated these effects, confirming a microbiota-dependent mechanism.
Among BER-responsive taxa, Bacteroides thetaiotaomicron (B.
Frontiers in Immunology published a clinical update in Infectious Disease on 01 Apr 2026.
The item focuses on Berberine protects against hypoxia-induced intestinal injury through modulation of gut microbiota and bile acid metabolism.
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